Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis

BACKGROUND: In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis. METHODS: TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA. RESULTS: We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7±9.3 ng/mL) than in samples from healthy individuals (10.5±5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis. CONCLUSION: The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.